What is the recommended treatment regimen for hepatitis C using Mavyret (glecaprevir and pibrentasvir)?

Mavyret Treatment Regimen for Hepatitis C

Mavyret (glecaprevir 300 mg/pibrentasvir 120 mg) should be taken as 3 tablets once daily with food for 8 weeks in treatment-naïve patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) across all HCV genotypes 1-6. 1

Treatment Duration by Patient Population

Treatment-Naïve Patients

• All genotypes (1-6) without cirrhosis: 8 weeks 1, 2
• All genotypes (1-6) with compensated cirrhosis (Child-Pugh A): 8 weeks 1, 2, 3

The EXPEDITION-8 trial demonstrated that 8-week treatment achieved 99.7% SVR12 in treatment-naïve patients with compensated cirrhosis across genotypes 1-6, establishing non-inferiority to the 12-week regimen 3. This represents a significant simplification compared to older guidelines that recommended 12 weeks for cirrhotic patients 2.

Treatment-Experienced Patients

For patients previously treated with NS5A inhibitors (without prior NS3/4A protease inhibitor):

• Genotype 1: 16 weeks (with or without cirrhosis) 1

For patients previously treated with NS3/4A protease inhibitors (without prior NS5A inhibitor):

• Genotype 1: 12 weeks (with or without cirrhosis) 1

For patients previously treated with peginterferon, ribavirin, and/or sofosbuvir (PRS) only:

• Genotypes 1,2,4,5,6 without cirrhosis: 8 weeks 1
• Genotypes 1,2,4,5,6 with compensated cirrhosis: 12 weeks 1
• Genotype 3 (with or without cirrhosis): 16 weeks 1, 2

Dosing and Administration

• Adult dose: 3 tablets (glecaprevir 300 mg/pibrentasvir 120 mg total) once daily with food 1
• Food requirement is critical: Glecaprevir plasma exposure increases 83-163% when taken with food compared to fasted state 2
• Pediatric patients ≥12 years or ≥45 kg: Same as adult dosing 1, 2
• Pediatric patients 3-11 years (<45 kg): Weight-based dosing using oral pellets 1

Special Populations

Renal Impairment

Mavyret is the treatment of choice for patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease on hemodialysis. 2, 4

• No dose adjustment required for any degree of renal impairment, including dialysis patients 1, 2, 5
• EXPEDITION-4 trial showed 98% SVR12 in patients with CKD stage 4-5 2
• Sofosbuvir-based regimens should be avoided in severe renal impairment due to metabolite accumulation 2, 4

Hepatic Impairment

Mavyret is absolutely contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) or any history of hepatic decompensation. 1, 2

• Glecaprevir exposure increases 2-fold in Child-Pugh A, 100% in Child-Pugh B, and 11-fold in Child-Pugh C cirrhosis 2
• For decompensated cirrhosis, use sofosbuvir/velpatasvir instead 2, 4

Transplant Recipients

• Liver or kidney transplant recipients: 12 weeks for most genotypes 1
• Genotype 1 NS5A-experienced or genotype 3 PRS-experienced: 16 weeks 1

HIV/HCV Coinfection

• Same treatment duration and regimen as HCV monoinfected patients 1, 2
• Carefully evaluate drug-drug interactions with antiretroviral therapy 2, 4

Pre-Treatment Requirements

Mandatory HBV screening before initiating Mavyret: Test for HBsAg and anti-HBc to identify risk of HBV reactivation 1, 2

• HBV reactivation has resulted in fulminant hepatitis, hepatic failure, and death in HCV/HBV coinfected patients 1
• Cirrhosis assessment using FIB-4 score, transient elastography, or clinical evidence 2
• Drug-drug interaction assessment is essential 2

Monitoring During Treatment

No routine laboratory monitoring is required during treatment due to high efficacy and low toxicity. 2, 6

• Monitor for hypoglycemia in diabetic patients on glucose-lowering medications 2
• Monitor INR in patients taking warfarin 2
• The SMART-C trial showed simplified monitoring (no on-treatment visits) achieved 92% SVR12, though this did not meet non-inferiority criteria compared to standard monitoring (95% SVR12) 6

Post-Treatment Assessment

• Confirm SVR12: HCV RNA testing at 12 weeks or later after treatment completion 2, 4
• Continue HCC surveillance: Patients with cirrhosis require ultrasound every 6 months indefinitely, even after achieving SVR 4, 7
• Assess for transaminase normalization and other causes of liver disease if elevated 2

Common Pitfalls and Contraindications

Critical contraindications:

• Moderate or severe hepatic impairment (Child-Pugh B or C) 1
• Any history of hepatic decompensation 1
• Concomitant use with atazanavir or rifampin (strong drug interactions) 1

Important caveats:

• Genotype 3 with compensated cirrhosis may have slightly lower SVR rates; consider alternative regimens (sofosbuvir/velpatasvir/voxilaprevir or sofosbuvir/velpatasvir plus ribavirin) for treatment-experienced patients 2
• Despite achieving SVR, cirrhotic patients remain at risk for HCC and require ongoing surveillance 4, 7
• The 8-week regimen for compensated cirrhosis is based on recent high-quality evidence and represents current best practice 3